crossing96/oncoscreening huggingface dataset:
Arsenic methylation and bladder cancer risk in case-control studies in Argentina and the United States.	OBJECTIVE: We sought to assess whether the metabolism of arsenic impacts a person's susceptibility to bladder cancer. METHODS: Urinary methylation products were measured in subjects from Argentina (114 cases and 114 controls) and the United States (23 cases and 49 controls). RESULTS: In Argentina, the adjusted odds ratio (OR) for subjects with a high proportion of ingested arsenic excreted as monomethylarsonate (%MMA) was 2.17 (95% confidence interval [CI] = 1.02-4.63) in smokers and 0.48 (95% CI = 0.17-1.33) in nonsmokers. In the United States, the adjusted ORs for high %MMA in subjects with arsenic intakes less than and greater than 100 microg/d were 1.20 (95% CI = 0.27-5.38) and 2.70 (95% CI = 0.39-18.6). CONCLUSIONS: Overall, these results are consistent with data from Taiwan suggesting that some individuals who excrete a higher proportion of ingested arsenic as MMA are more susceptible to arsenic-related cancer.	bladder
[A case of secondary malignant lymphoma of the urinary bladder].	A 56-year-old man was admitted to our hospital for salvage chemotherapy of recurrent diffuse large B cell malignant lymphoma at clinical stage IIIb and which had been treated with 6 cycles of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP). Computed tomography showed multiple tumors in the bladder after a cycle of ifosfamide, etoposide and mitoxantrone (MINE), but cystoscopy after the second cycle revealed a single non-papillary tumor about 1cm in diameter. After 3 cycles of MINE therapy, transurethral resection of bladder tumor was performed. At the time of the operation, the protruded lesion disappeared and there remained only a scar. Biopsy of the scar revealed malignant lymphoma infiltrated into the submucosal layer. Although the rate of the bladder involvement of malignant lymphoma reaches 3-20% in autopsy cases, it is very rare for a secondary malignant lymphoma of the urinary bladder to be diagnosed clinically. The prognosis of the secondary bladder lymphoma is much poorer than that of the primary one, because of the widespread dissemination of the disease at the time of diagnosis.	bladder
Molecular basis for the involvement of thymidine phosphorylase in cancer invasion.	Thymidine phosphorylase (TP), also known as platelet-derived endothelial cell growth factor (PD-ECGF), has been implicated in bladder cancer angiogenesis and invasion. However, the molecular basis of its role in invasion remains unclear. We investigated the expression of TP and 10 invasion-related genes in bladder cancers from 72 randomly selected patients by real-time two-step RT-PCR assay. We found that the expression levels of TP, MMP-9, uPA, and MMP-2 were significantly higher in invasive tumors than those in superficial tumors. Also, the expression level of TP significantly correlated with that of uPA, MMP-1, MMP-9, PAI-1 and VEGF. KK47/TP cells, bladder cancer cells that overexpress TP, had a higher expression of MMP-7 and MMP-9 than KK/CV cells that express lower level of TP in hypoxic condition. PC/TP cells, prostate cancer cells that overexpress TP, also had a higher expression of MMP-1 and MMP-7 than PC/CV cells that express no detectable TP. Taken together these data indicate that TP enhances the invasion of tumor cells through the induction of invasion-related genes.	bladder
Transitional cell bladder tumor: predicting recurrence and progression by analysis of microsatellite loss of heterozygosity in urine sediment and tumor tissue.	Transitional cell bladder tumors (TCT) is prone to recurrence (60-80%) after tumor resection. Up to 25% of these patients will progress, so it is important to find reliable predictive markers. We analyzed for loss of heterozygosity (LOH) with respect to 13 microsatellites located on 10 different chromosomal arms. This analysis was performed on the urine sediment and tumor tissue from 59 patients with bladder TCT and on the urine and normal-looking mucosa from 25 patients with a history of bladder TCT but no evidence of disease at the time of the study inclusion. The median follow-up period was 23.1 months (range, 2-48 months) for the 59 patients with bladder TCT and 25 months (range, 4-57 months) for the 25 patients without evidence of ongoing active disease. Correlation between LOH and eventual recurrence, progression, and mortality was investigated. In patients with noninvasive TCT, correlation between 11p tumor tissue LOH and recurrence was found. Similarly, 8p LOH in both urine sediment and tumor tissue correlated with progression. Finally, in the group of patients with a history of bladder TCT, normal tissue 8p and/or 11p LOH correlated with recurrence.	bladder
HYTAD1-p20: a new paclitaxel-hyaluronic acid hydrosoluble bioconjugate for treatment of superficial bladder cancer.	OBJECTIVE: To report the development of a new water-soluble paclitaxel-hyaluronic acid bioconjugate, HYTAD1-p20, for intravesical treatment of superficial bladder cancer. MATERIALS AND METHODS: HYTAD1-p20 was synthesized by carboxyl esterification of hyaluronic acid with paclitaxel, and its physicochemical and biologic properties were characterized. RESULTS: Paclitaxel loading was optimized at 20% w/w; this procedure increased by 500-fold the paclitaxel concentration in the resulting water-soluble biomaterial. In vitro, HYTAD1-p20 exerted a much higher dose-dependent inhibitory effect against RT-4 and RT-112/84 bladder carcinoma cell growth than that of free drug, and directly interacted with CD44 expressed by bladder tumor cells. In vivo, results of pharmacokinetic studies performed in mice after bladder catheterization and intravesical instillation of HYTAD1-p20 disclosed that drug leakage was negligible during a 2-hour analysis. Histologic examination of drug-instilled bladders revealed that HYTAD1-p20 was extremely well tolerated, while paclitaxel alone produced mucosal disruption and submucosal infiltration of inflammatory cells. Treatment of severe combined immunodeficient mice bearing subcutaneous RT-112/84 tumors with maximum tolerated doses of bioconjugate or paclitaxel showed that HYTAD1-p20 exerted a therapeutic activity comparable to that of free drug. CONCLUSIONS: These data suggest that HYTAD1-p20 significantly improved results obtained with conventional paclitaxel in terms of hydrosolubility, in vitro activity against human bladder cancer cells, and in vivo biocompatibility. This bioconjugate is a potentially useful treatment for superficial urothelial malignancy.	bladder
Dimethylarsinic acid: results of chronic toxicity/oncogenicity studies in F344 rats and in B6C3F1 mice.	Dimethylarsinic acid (DMA(V), cacodylic acid), a foliar herbicide, was administered in the diet to B6C3F1 mice (at dose levels of 0, 8, 40, 200, and 500 ppm) and to F344 rats (at dose levels of 0, 2, 10, 40, and 100 ppm) for 2 years, according to US EPA guidelines. In mice, there were no treatment-related tumors observed at any site. Treatment-related progressive glomerulonephropathy and nephrocalcinosis were observed in the kidneys in both sexes. The incidence of vacuolation of the epithelium in the urinary bladder was increased in both sexes, but was not associated with cytotoxicity, necrosis or hyperplasia. Based on non-neoplastic lesions found in the urinary bladder, the NOEL for mice was assessed to be 40 ppm in males and 8 ppm in females. In rats, treatment-related mortality occurred early in the study in five males in the 100 ppm group and in one male in the 40 ppm group. Papillomas and carcinomas with degeneration of the urothelium, necrosis and urothelial cell hyperplasia, were found in the urinary bladders of both sexes. In male rats, one papilloma was found in each of the 10 and 40 ppm groups; one urothelial cell carcinoma was found in the 2 ppm group and two in the 100 ppm group. Four papillomas and six urothelial cell carcinomas were found in the female 100 ppm group. Non-neoplastic treatment-related kidney lesions were confined to the 40 and 100 ppm levels and included necrosis, pyelonephritis, medullary nephrocalcinosis and tubular cystic dilation, hyperplasia of the epithelial lining of the papilla, and pelvic urothelial cell hyperplasia. All of these kidney changes appear to be related to an increase in the aging nephropathy of the rat. Dose-related increases in the height of the thyroid follicular epithelium were also noted in males and females, however, such changes reflect an adaptive response of the thyroid to decreased levels of circulating thyroid hormone, rather than an adverse effect. Based on the kidney and bladder lesions, the NOEL for non-neoplastic and neoplastic lesions was considered to be 10 ppm in males and females. Based on these studies, DMA(V) is carcinogenic only in rats and only at relatively high doses, with the urinary bladder as the target organ. Female rats appear to be more sensitive to the effects of DMA(V) than male rats. DMA(V) is not carcinogenic in mice.	bladder
Angiotensin II type 1 receptor antagonist candesartan as an angiogenic inhibitor in a xenograft model of bladder cancer.	PURPOSE: There have been several studies on the antitumor activity of angiotensin II type 1 receptor (AT1R) antagonists. In this study, we evaluated the efficacy of the AT1R antagonist candesartan in bladder cancer. EXPERIMENTAL DESIGN: For the study in vitro, human bladder cancer cells (KU-19-19) were cultured with or without angiotensin II and candesartan. Various cytokines and cell viability were analyzed. For the study in vivo, a tumor xenograft model was prepared in nude mice using KU-19-19 cells. Mice were given candesartan daily by oral gavage. Microvessel density, expression of vascular endothelial growth factor (VEGF), and apoptosis were assessed. RESULTS: Candesartan did not induce direct toxicity in KU-19-19 cells, but VEGF and interleukin-8 were significantly lower in candesartan-treated cells (2.55 +/- 0.25 and 6.58 +/- 0.48 pg/10(3) cells) than in the angiotensin II-treated control cells (3.16 +/- 0.42 and 7.91 +/- 0.69 pg/10(3) cells). In mice, candesartan both at doses of 2 and 10 mg/kg/d significantly suppressed tumor growth in mice (35.4% and 33.5% reduction in tumor volume). Microvessel density was significantly decreased by candesartan (9.8 +/- 2.8 per field) compared with the control group (17.6 +/- 6.0 per field), and VEGF expression was significantly suppressed by this AT1R antagonist. However, candesartan did not induce apoptosis of cancer cells in the tumor. CONCLUSIONS: Specific blockade of AT1R prevented bladder tumor growth by inhibiting angiogenesis. However, its antitumor effect was not due to direct toxicity. Because AT1R antagonists are widely used to treat hypertension, and a 2 mg/kg/d dose level of candesartan is clinically achievable, this AT1R antagonist could also be used to treat bladder cancer.	bladder
Biological characteristics in bladder cancer depend on the type of genetic instability.	PURPOSE: Malignant tumors show an inherent genetic instability that can be classified as microsatellite instability (MSI) or chromosomal instability (CIN). To elucidate the differences in biological characteristics of bladder cancer between the two types of genetic instability, the expression of the mismatch repair (MMR) proteins, Aurora-A and p53 proteins, the number of centrosomes, numerical aberrations of chromosomes and 20q13, and DNA ploidy were examined in 100 human urothelial carcinomas of the bladder. EXPERIMENTAL DESIGN: Expressions of the MLH1, MSH2, Aurora-A, and p53 proteins and the numbers of centrosomes were immunohistochemically assessed. Numerical aberrations of chromosomes 7, 9, 17, and 20q13 spots were evaluated by fluorescence in situ hybridization, and DNA ploidy was assessed by laser scanning cytometry. RESULTS: The expression levels of the MMR related-proteins decreased in 9 of 100 tumors. Tumors with low MLH1 or MSH2 expression (designated as MSI cancers) were not linked with centrosome amplification, Aurora-A overexpression, increased p53 immunoreactivity, 20q13 gain, DNA aneuploidy, and disease progression. MSI cancers showed a favorable prognosis. CIN cancers (49 cases), defined as tumors with a large intercellular variation in centromere copy numbers, were associated more frequently with centrosome amplification, Aurora-A overexpression, increased p53 immunoreactivity, and 20q13 gain than the others (51 cases). Tumors with disease progression were included in the CIN cancer group. CONCLUSIONS: The present observations suggest that there are differences in the biological characteristics of the two types of genetic instability.	bladder
Pelvic chemoradiotherapy after chemotherapy for metastatic bladder cancer.	OBJECTIVE: Consolidative radiotherapy has improved local control in other tumors with high local recurrence rates but has not been well studied in urothelial cancer. We hypothesized that pelvic chemoradiotherapy (PCRT) given after systemic chemotherapy for metastatic bladder cancer (MTCC) might alter the pattern of disease recurrence, and reduce the complications and morbidity of intrapelvic disease relapse. A 74% locoregional relapse rate has been observed in MTCC patients with intrapelvic nodal disease after response to chemotherapy. To explore this hypothesis further, we performed a retrospective analysis and report the efficacy, toxicity and pattern of failure with this approach. MATERIALS AND METHODS: Patients treated for MTCC who received consolidative PCRT following at least a partial response to systemic chemotherapy were identified and their charts reviewed for pelvic relapse, disease progression, survival, and toxicity. RESULTS: Twelve patients were identified and median follow-up was 15.6 months. Nine patients developed progressive disease and died, and median survival was 15.6 months. Three patients had pelvic progression (pelvic failure rate 25%). Median time to pelvic failure was 12.8 months. At last follow-up, three patients were alive and disease-free. No life-threatening toxicities were observed. The most common acute non-hematological toxicities were diarrhea and nausea. CONCLUSIONS: These data support a hypothesis that consolidative PCRT following chemotherapy in MTCC patients with systemic disease control may be feasible and efficacious for improving pelvic disease control. This intervention should be considered for further study in prospective controlled clinical trials.	bladder
[The active search for occupational cancer cases: bladder cancer in Lombardy Region].	OBJECTIVE: A study called OCCAM (OCcupational CAncer Monitoring) has been carried out in order to establish a nationwide surveillance system for occupational cancer. This project consists of population-based case control studies where information on past occupations are automatically gathered National Institute for Social Security's archive, cancer cases are obtained from Cancer Registries (CR) and controls are sampled from population files of the National Health Service. As previous results obtained using CR were encouraging, we tried to use regional hospital discharge records as a source of incident cases. DESIGN: We have conducted a population based case-control study with 1568 male bladder cancer cases occurred in the years 1999 and 2000 and 18818 controls randomly sampled from resident population in Lombardy region (Italy). RESULTS: Despite the limits of this approach the following industries were found at increased risk of bladder cancer: leather and shoes industry (OR=1.83; CI 90%: 1.01-3.33; observed: 10); transports (OR=1.28; CI 90%: 0.94-1.76; observed: 37), rubber industry (OR=1.22 CI 90% 0.80-1.85; observed: 19) and printing industry (OR=1.5 CI 90%: 1.10-2.05; observed: 38). CONCLUSION: The ability of OCCAM surveillance system to find known associations using routinely available data offers new opportunities to detect cancer cases likely to be of occupational origin.	bladder
Potent activation of mitochondria-mediated apoptosis and arrest in S and M phases of cancer cells by a broccoli sprout extract.	We have previously shown that broccoli sprouts are a rich source of chemopreventive isothiocyanates, which potently induce carcinogen-detoxifying enzymes and inhibit the development of mammary and skin tumors in rodents. However, the principal isothiocyanate present in broccoli sprout extracts, sulforaphane, not only induces carcinogen-detoxifying enzymes but also activates apoptosis and blocks cell cycle progression. In this article, we show that an aqueous extract of broccoli sprouts potently inhibits the growth of human bladder carcinoma cells in culture and that this inhibition is almost exclusively due to the isothiocyanates. Isothiocyanates are present in broccoli sprouts as their glucosinolate precursors and blocking their conversion to isothiocyanates abolishes the antiproliferative activity of the extract. Moreover, the potency of isothiocyanates in the extract in inhibiting cancer cell growth was almost identical to that of synthetic sulforaphane, as judged by their IC50 values (6.6 versus 6.8 micromol/L), suggesting that other isothiocyanates in the extract may be biologically similar to sulforaphane and that nonisothiocyanate substances in the extract may not interfere with the antiproliferative activity of the isothiocyanates. Further study showed that the isothiocyanate extract of broccoli sprouts activated the mitochondria-mediated apoptosis pathway and halted cells in S and M phases. Cell cycle arrest was associated with down-regulation of Cdc25C and disruption of mitotic spindles. These data show that broccoli sprout isothiocyanate extract is a highly promising substance for cancer prevention/treatment and that its antiproliferative activity is exclusively derived from isothiocyanates.	bladder
Concurrent diagnosis of urothelial carcinoma and squamous cell carcinoma of the bladder in a patient with a vesicorectal fistula from invasive rectal cancer.	A 47-year-old man underwent a low anterior resection of the rectosigmoid colon with en bloc cystoprostatectomy for vesicorectal fistula due to a locally advanced rectal cancer. Histopathological examination of the bladder revealed two additional primary malignancies: urothelial carcinoma and squamous cell carcinoma. To our knowledge, this is the first reported case of two histologically distinct urothelial malignancies that were diagnosed during a work up of vesicorectal fistula due to adenocarcinoma of the rectum.	bladder
Regularly methylated novel pro-apoptotic genes associated with recurrence in transitional cell carcinoma of the bladder.	Epigenetic silencing of tumor suppressor genes by promoter hypermethylation has been shown for a variety of genes in bladder cancer. Various p53 target genes have been investigated, but only few demonstrated promoter hypermethylation when semiquantitative detection methods were applied. To address to the question whether promoter methylation of novel p53 effector genes is a common event in transitional cell carcinoma of the bladder, we selected the p53 target genes apoptotic protein-activating factor (APAF-1), Caspase 8 (CASP-8), death-associated protein kinase, (DAPK-1) and insulin-like growth-factor-binding protein-3 (IGFBP-3), performing quantitative methylation-specific real-time PCR. The individual level of methylation (normalized index of methylation) was correlated with clinicopathological features as well as the biological behavior of the superficial and muscleinvasive tumors. Tissue was obtained from 110 tumor patients and 20 patients without urological malignancy. The median follow-up of the tumor patients was 52 months. Hypermethylation of the promoter region in tumor specimens was common for APAF-1 (100%), DAPK-1 (74%) and IGFBP-3 (66%), but not for CASP-8 (3.6%). It was seen less frequently and with undetectable or low methylation levels in the normal urothelium group. The APAF-1 methylation levels significantly correlated with tumor stage and tumor grade. The APAF-1 and IGFBP-3 methylation levels were able to separate tumors with higher recurrence risk from low-risk tumors in nonmuscleinvasive and muscleinvasive tumors. In multivariate analysis, APAF-1 and IGFBP-3 methylation levels were independent prognostic markers for recurrence in superficial bladder tumors. This study provides new insights into the role of promoter methylation of selected p53 target genes. The extent of promoter methylation of specific genes offers additional prognostical information and is associated with the outcome in patients with nonmuscleinvasive and muscleinvasive bladder cancer.	bladder
Stage-associated overexpression of the ubiquitin-like protein, ISG15, in bladder cancer.	Bladder cancer is among the most prevalent malignancies, and is characterised by frequent tumour recurrences and localised inflammation, which may promote tissue invasion and metastasis. Microarray analysis was used to compare gene expression in normal bladder urothelium with that in tumours at different stages of progression. The innate immune response gene, interferon-stimulated gene 15 kDa (ISG15, GIP2), was highly expressed at all stages of bladder cancer as compared to normal urothelium. Western blotting revealed a tumour-associated expression of ISG15 protein. ISG15 exhibited a stage-associated expression, with significantly (P<0.05) higher levels of ISG15 protein in muscle-invasive T2-T4 tumours, compared with normal urothelium. Although ISG15 is involved in the primary immune response, ISG15 expression did not correlate with bladder inflammation. However, immunohistochemical staining revealed expression of ISG15 protein in both cancer cells and stromal immune cells. Interestingly, a significant fraction of ISG15 protein was localised to the nuclei of tumour cells, whereas no nuclear ISG15 staining was observed in ISG15-positive stromal cells. Taken together, our findings identify ISG15 as a novel component of bladder cancer-associated gene expression.	bladder
N-acetylglucosaminyltransferase V and beta1-6 branching N-linked oligosaccharides are associated with good prognosis of patients with bladder cancer.	PURPOSE: N-acetylglucosaminyltransferase V (GnT-V) is an enzyme that catalyzes beta1-6 branching of N-acetylglucosamine on asparagine (N)-linked oligosaccharides (N-glycan) of cell proteins. We examined the relationship between GnT-V expression and clinicopathologic features of the patients with bladder cancer. EXPERIMENTAL DESIGN: We immunohistochemically examined GnT-V expression in paraffin-embedded bladder cancer specimen using anti-GnT-V monoclonal antibody. We compared GnT-V expression with cause-specific survival of the patients with bladder cancer treated by radical cystectomy. Kaplan-Meier survival curves were generated to show the cause-specific survival. Univariate and multivariate analyses were carried out to compare GnT-V expression with other clinical and pathologic variables. We also evaluated mRNA expression of GnT-V and N-linked oligosaccharide structure in bladder cancer specimens. RESULTS: Immunohistochemistry revealed that GnT-V expression inversely correlated with tumor grade and stage. The incidence of positive GnT-V expression in bladder cancer was significantly higher in low-grade/superficial cancer than in high-grade/invasive cancer. The patients whose tumor was positive for GnT-V survived significantly longer than those whose tumor was negative for GnT-V. Univariate and multivariate analyses revealed that GnT-V expression was an independent predictor of prognosis of the patient. The expression of GnT-V mRNA determined by reverse transcription-PCR was consistent with the results with immunohistochemistry for tumor samples. Carbohydrate structural analysis revealed that superficial bladder cancer is rich in branched N-linked oligosaccharides, for which biosynthesis GnT-V is responsible. CONCLUSIONS: GnT-V and its resultant beta1-6 branching N-linked oligosaccharides are closely related to low malignant potential and good prognosis of the patients with bladder cancer.	bladder